Pancreatic cancer in Syrian hamsters was enhanced when high levels of dietary fat (corn oil) were fed after a single dose of the pancreatic carcinogen N-nitrosobis-(2-oxopropyl)amine (BOP). Studies in humans have suggested that populations consuming high fat diets are at elevated risk of pancreatic cancer development. Investigations proposed in this application are designed to clarify the role of dietary fat in pancreatic carcinogenesis and thereby to assist in providing a basis for formulating dietary recommendations for humans. The earlier results in pancreatic carcinogenesis in hamsters have led to three fundamental queations. 1) Was the enhancing effect of the diet related to the fat per se or rather to the increased calorie intake of the animals fed high fat diets? 2) Is the type of fat important in the promotion of pancreas cancer, as shown for other types of experimental and human cancer? 3) By what mechanism does dietary fat promote cancer in the pancreas? This application proposes studies to answer these questions by 1) a pair-feeding study which will determine if the effect of dietary fat on the induction of pancreatic cancer by BOP in hamsters is due to the increased calories consumed, which caused inceased body weight, or to other properties of fat which is more likely and 2) comparing the effects of a saturated fat (beef tallow) with those of corn oil to determine if the type of fat is a factor in pancreatic cancer development. A mixture of beef tallow and corn oil will also be evaluated to determine the effect of combining the two types, since human fat consumption consists of several types of fat. The third question will be addressed by examining membrane phospholipid content, and cellular calcium-dependent-phospholipid-dependent protein kinase activity, phospholipase A2 activity and prostaglandin production in hamsters fed low and high fat diets. These enzymes will be measured because of their suggested roles as targets of tumor promoters and because of their dependence on membrane phospholipid.